The ability to control transport of chemical species across cellular membranes is important from a therapeutic standpoint inasmuch as a number of disease conditions, including glaucoma and certain kidney and stomach disorders, are directly related to such transport. In addition, a better understanding of the mechanisms for such transport can be expected to yield improved therapeutic and diagnostic tools.
It is thought that transport of ions across membranes, as for example K.sup.+ and Cl.sup.- ions, is controlled in part by membrane channel proteins which exist in certain membranes and which act to transport or "channel" ions across such membranes. Agents which selectively block ion transport have been described, as for example furosemide (an anion blocker, U.S. Pat. No. 3,058,882) and quinine (a cation blocker). Furosemide is widely thought to interact with a hypothetical sodium/potassium/dichloride "cotransporter" (as distinct from a channel protein), while quinine is thought to block K.sup.+ channels. Only about six or so channel proteins have actually been isolated, and each of these is thought to transport only a single ionic species (e.g., K.sup.+ or Cl.sup.-, but not both).
The present invention involves, in part, a newly discovered channel protein responsible for membrane transport of both K.sup.+ and/Cl.sup.- ions. It has been further discovered that quinine, furosemide and certain new furosemide derivatives are capable of binding to this K.sup.+ /Cl.sup.- channel protein, thereby blocking both K.sup.+ and Cl.sup.- transport as controlled by that specific channel protein. By utilizing such channel protein binding compounds in affinity gels, it has been shown in investigations relating to the present invention to be possible to isolate and purify the channel protein. The channel protein and the binding compounds are useful in therapeutic control of membrane transport and in developing assays related to membrane control.